MC148 encoded by human molluscum contagiosum poxvirus is an antagonist forhuman but not murine CCR8

The viral CC chemokines MC148, encoded by the poxvirus molluscum. contagios um, and viral macrophage inflammatory protein (vMIP)-I and vMIP-II, encoded by human herpesvirus 8, were probed on the murine CC receptor (CCR) 8 in p arallel with human CCR8. In calcium mobilization assays, vMIP-I acted as a high-affinity agonist, whereas vMIP-II acted as a low-affinity antagonist o n the murine CCR8 as well as the human CCR8. MC148 was found to bind and bl ock responses through the human CCR8 with high affinity, but surprisingly M C148 was unable to bind and block responses through the murine CCR8. Becaus e MC148 is the only high-affinity antagonist known to target and be selecti ve for CCR8, MC 148 is a valuable tool to decipher the role played by CCR8 in the immune system. This study shows that MC148 could not be used in muri ne inflammatory models; however, it will be interesting to see whether it c an be used in other animal models to delineate the role played by CCR8.